Severe pneumocranium after gamma knife stereotactic radiosurgery for brain metastasis: A case report and literature review

Rationale: Gamma knife stereotactic radiosurgery (GKRS) is a recognized safe and effective treatment for brain metastasis; however, some complications can present significant clinical challenges. This case report highlights a rare occurrence of cerebrospinal fluid (CSF) leakage and pneumocranium following GKRS, emphasizing the need for awareness and prompt management of these complications. Patient concerns: A 35-year-old male with a history of malignant neoplasm of the lip in 2015 and perineural spread of malignancy into the left cavernous sinus was treated with GKRS in 2017. The patient was admitted emergently 39 days after discharge due to persistent headache and dizziness. Diagnoses: Brain computed tomography (CT) revealed diffuse bilateral pneumocranium alongside an observation of CSF leakage. Interventions: A surgical procedure involving a left frontal-temporal craniotomy was performed to excise a residual skull base tumor and repair the dura, guided by a navigator system. The conclusive pathological assessment revealed the presence of squamous cell carcinoma markers. Outcomes: The patient exhibited excellent tolerance to the entire procedure and experienced a prompt and uneventful recovery process. After surgery, the symptoms alleviated and CSF leak stopped. The follow-up image showed the pneumocranium resolved. Lessons: Pneumocranium due to early-stage post-GKRS is uncommon. The rapid tumor shrinkage and timing of brain metastasis spreading through the dura can lead to CSF leak and pneumocranium. We reviewed current treatment options and presented a successful craniotomy-based dura repair case.


Introduction
Brain metastases are adults' most common type of intracranial neoplasm. [1,2]Brain metastases develop when malignant cells from a primary site migrate to the brain.While brain metastases can stem from diverse locations and cancer types, those originating in the breast, colon, kidney, lung, and melanoma generally possess an elevated likelihood of inducing brain metastases. [3]rain tumor surgery presents the challenge of removing as many tumors as possible while minimizing damage to healthy brain tissue. [4,5]Excision surgery is considered the most effective treatment for solid tumors. [6]However, craniotomy may not consistently achieve the desired outcome ideally. [7]As a result, advanced technologies have been developed for brain cancer treatment.
10] This noninvasive technique delivers highly focused gamma rays to specific intracranial targets, achieving remarkable precision while sparing surrounding healthy brain tissue. [8]n spite of its well-established advantages and overall safety profile, there are documented instances of complications reported after undergoing GKRS. [11,12]he potential complications after GKRS can vary depending on the specific condition being treated and the location of Written informed consent was secured from the patient for publication of this report.
][15] Possible resolvable complications include swelling, edema, nausea and vomiting, headache, fatigue, hair loss, and visual or auditory disturbances.However, more severe complications such as seizures, radiation necrosis, radiation-induced tumors, and pneumocranium require immediate treatment.
Here, we present a case of severe pneumocranium subsequent to GKRS for brain metastasis in a patient.Additionally, a comprehensive literature review was conducted to draw a comparison with the current case.

Case report
The patient was a 35-year-old man with a previous diagnosis of left lip cancer, classified explicitly as pT2N2bM0.In 2015 to 2016, the patient underwent a composite resection for left upper lip cancer, which involved sacrificing the affected skin, performing an inferior maxillectomy, and a marginal mandibulectomy.Additionally, the patient underwent a left modified radical neck dissection and a right selective neck dissection.Following the surgery, free flap reconstruction performed.Since the procedure, the patient has regularly attended follow-up appointments at our ear, nose, and throat outpatient department (OPD).
The patient had been experiencing left ptosis (drooping eyelid) and eye protrusion for 2 weeks before seeking medical advice.He sought medical attention at the oncology OPD and was subsequently referred to the Neurosurgery OPD for comprehensive assessment in 2017.Neurological examination revealed the Glasgow Coma Scale score of E4V5M6, and the pupil sizes were measured at 4.0+ for the right eye and 3.5− for the left eye.Muscle power was found to be intact in all tested muscles.The patient mentioned experiencing a similar episode about 2 years ago, during which he had recovered well.
Considering the clinical presentation, our primary impressions include left ptosis, which could suggest brain metastasis or carotid-cavernous fistula.The patient was admitted to our medical ward as part of the evaluation and management process.Magnetic resonance imaging and Orbit computed tomography (CT) scan showed evidence of perineural spread of malignancy originating from the left skull base, extending into the cavernous sinus, and causing bony destruction of the left sphenoid wing (Fig. 1A and B).
Upon admission, GKRS was promptly scheduled for the patient on the second day.During the procedure, we identified a left skull base tumor with invasion into the cavernous sinus, measuring approximately 21.3 cc.The treatment plan involved applying a 50% marginal dose of 16 Gy, with a mean dose of 19.6 Gy.We used 18 mm and 14 mm collimators with plugs to perform the radiosurgery.The entire procedure lasted approximately 1.5 hours.Following the radiosurgery, the patient experienced eye swelling on the first day after the operation.In response, we prescribed dexamethasone to manage the swelling and provided pain control measures.Subsequently, by the fourth day of admission, the patient condition had shown significant improvement, allowing for discharge from the hospital with plans for follow-up at our OPD.
At 39 days following discharge, the patient was urgently taken to the emergency department (ED) due to ongoing complaints of persistent headache and dizziness.Physical examination revealed increased intracranial pressure and meningeal signs, indicating possible involvement of the protective membrane covering the brain (dura).A Brain CT scan showed severe pneumocranium (Fig. 1C-F).Based on these findings, the provisional diagnosis was a cerebrospinal fluid (CSF) leak with pneumocranium.
In response to the critical condition, the patient was promptly admitted for emergent surgery to repair the dura.The surgical procedure performed was a left frontotemporal craniotomy, removing a tumor at the skull base.In immunohistochemical analysis, the specimen showed positive for cytokeratin and p40, marker of squamous cell carcinoma.The tumor was situated in the left temporal region and had caused a defect in the dura, extending further into the lateral sphenoid sinus.The surgical approach was guided using a navigator, and an external ventricular drain was also utilized during the operation.After surgery, the headache and dizziness symptoms were alleviated, and the CSF leak stopped.The follow-up CT image by the eleventh day postoperatively showed the pneumocranium was no longer present (Fig. 2).The patient was discharged with plans for follow-up at our OPD.

Discussion
A 35-year-old man with a history of left lip cancer was diagnosed with brain metastasis at the skull base and treated by GKRS.The patient recovered well and was released.The patient was admitted 39 days after discharge with persistent headache and dizziness.A Brain CT scan showed severe pneumocranium, likely caused by CSF leakage.The patient received emergent surgery to repair the dura.After the surgery, the symptoms of headache and dizziness were alleviated, the CSF leak stopped, and pneumocranium resolved.Close monitoring was maintained.
CSF fills the cranial cavity to protect the brain and spinal cord from damage from the outside.When the dura mater, the outermost tissue surrounding the CSF, is broken, CSF may leak from the cranial space.CSF leakage is a known but infrequent complication in conventional transsphenoidal surgery, with reported incidence rates ranging from 0.4% to 9%. [16,17]onversely, CSF leakage had been rarely documented in noninvasive surgical procedures like GKRS.Kim et al [18] reported a case of CSF leakage occurring 4 months after GKRS in a patient with skull base metastasis.
Similarly, Ogawa et al [19] described a case of CSF leakage ten years after a combination of transsphenoidal surgery and GKRS in a patient with prolactin-secreting pituitary adenoma.Two other patients with pituitary adenoma underwent transsphenoidal surgery followed by GKRS and experienced CSF leakage 2 and 7 years after GKRS, respectively. [20]Another case of CSF leakage was reported in a cohort of 32 patients with malignant skull base tumors. [21]Although the incidence of CSF leakage after GKRS is very low, as demonstrated in these cases, it remains a significant complication that requires careful consideration.
When air enters the cranial space, it is called pneumocephalus.About 25% of patients with pneumocephalus were caused by factors other than trauma. [22,23]One of these factors was a tumor at the skull base.Metastasis cancer corrodes or invades the surrounding tissue.Since the dura thickness in the skull base was relatively thinner than other parts, [24] it was easier for cancer cells to breach the CSF leak-proof mechanism in the skull base.[27][28] This scenario was described in several clinical case reports (Fig. 3). [29,30]llock et al [31] reported that the size of nonfunctioning pituitary adenomas decreased in 60% of patients after gamma knife surgery.The mean volume reduction in vestibular schwannomas after GKRS was 31%. [32]This indicated that although the primary goal of GKRS was suppressing tumor growth, the tumor did shrink after GKRS.Once the tumor shrank and exposed the defects caused by tumor erosion in the dura, CSF may start leaking immediately.Although rare, this had been reported after dopaminergic agonists treated prolactinoma, [33] after spine tumor resection, [34] and after GKRS. [32]These reports indicated that the shrink-and-leak scenario might be the mechanism behind observed pneumocranium after GKRS for brain metastasis.

Limitations
Our study is subject to several limitations.Firstly, being a single case report, the findings may not be generalizable.Secondly, the proposed mechanism for the development of pneumocranium is speculative.Third, the relatively short follow-up period may not fully capture long-term outcomes or recurrent complications.These limitations highlight the need for more extensive studies to validate and expand upon these findings.

Conclusion
Although rare, pneumocranium can occur after GKRS.If a patient complains about new or worsening symptoms, pneumocranium should be suspected and checked immediately after therapy.

Figure 1 .
Figure 1.MRI and CT images at different times during the therapy.MRI image was taken at pre-and post-GKRS (A, B).Bone (C, D) and brain (E, F) view of CT pre-and after left frontotemporal (F-T) craniotomy.CT = computed tomography, GKRS = gamma knife stereotactic radiosurgery, MRI = magnetic resonance imaging.

Figure 2 .
Figure 2. CT image on the 11th day following craniotomy.CT = computed tomography.